Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Linc01116 Silencing Inhibits the Proliferation and Invasion, Promotes Apoptosis of Chordoma Cells via Regulating the Expression of Mir-9-5p/PKG1

Author(s): Junqi Liu, Yan Qi, Siyuan Hou, Siyuan Zhang and Zhenlin Wang*

Volume 24, Issue 8, 2024

Published on: 12 September, 2023

Page: [1056 - 1071] Pages: 16

DOI: 10.2174/1566524023666230719121758

Price: $65

conference banner
Abstract

Background: Long intergenic non-protein coding RNA 1116 (LINC01116) plays a carcinogenic role in a variety of cancers. The study aims to investigate the roles of LINC01116 and hsa-miR-9-5p (miR-9-5p) and fathom their interaction in chordoma.

Methods: The predicted binding sites between miR-9-5p with LINC01116 and phosphoglycerate kinase 1 (PGK1) by starBase were confirmed through dual-luciferase reporter assay. The behaviors of chordoma cells undergoing transfection with siLINC01116 or miR-9-5p inhibitor were determined by Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and flow cytometry assays. The glucose consumption, lactate production, and adenosine triphosphate (ATP) production of chordoma cells were examined with specific kits. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to determine relevant gene expressions in chordoma cells.

Results: Silencing of LINC01116 facilitated the apoptosis and expressions of Bcl-2- associated X (Bax), cleaved caspase-3 (C caspase-3) and miR-9-5p while repressing the cell cycle, viability, proliferation, invasion, glucose consumption, lactate production, ATP production, and expressions of PGK1 and Bcl-2. Meanwhile, LINC01116 sponged miR-9-5p, which could target PGK1. Moreover, the miR-9-5p inhibitor acted contrarily and reversed the role of siLINC01116 in chordoma cells. Besides, LINC01116 downregulation facilitated apoptosis and attenuated the proliferation and invasion of chordoma cells as well as PGK1 expression by upregulating miR-9-5p expression.

Conclusion: LINC01116/miR-9-5p plays a regulatory role in the progression of chordoma cells and is a potential biomarker for chordoma.

Keywords: LINC01116, miR-9-5p, chordoma, PGK1, glycolysis, CCK-8.

[1]
Harsh GR IV, Vaz-Guimaraes F. Chordomas and chondrosarcomas of the skull base and spine. Massachusetts: Academic Press 2017.
[2]
Youssef C, Aoun SG, Moreno JR, Bagley CA. Recent advances in understanding and managing chordomas. F1000 Res 2016; 5: 2902.
[http://dx.doi.org/10.12688/f1000research.9499.1] [PMID: 28105324]
[3]
Pillai S, Govender S. Sacral chordoma: A review of literature. J Orthop 2018; 15(2): 679-84.
[http://dx.doi.org/10.1016/j.jor.2018.04.001] [PMID: 29881220]
[4]
Whelan JS, Davis LE. Osteosarcoma, Chondrosarcoma, and Chordoma. J Clin Oncol 2018; 36(2): 188-93.
[http://dx.doi.org/10.1200/JCO.2017.75.1743] [PMID: 29220289]
[5]
Schwab JH, Healey JH, Rose P, Casas-Ganem J, Boland PJ. The surgical management of sacral chordomas. Spine 2009; 34(24): 2700-4.
[http://dx.doi.org/10.1097/BRS.0b013e3181bad11d] [PMID: 19910774]
[6]
Meng T, Jin J, Jiang C, et al. Molecular targeted therapy in the treatment of chordoma: A systematic review. Front Oncol 2019; 9(30): 30.
[http://dx.doi.org/10.3389/fonc.2019.00030] [PMID: 30775316]
[7]
Casali PG, Messina A, Stacchiotti S, Tamborini E, Crippa F, Gronchi A. Imatinib mesylate in chordoma. Cancer 2004; 101(9): 2086-97.
[http://dx.doi.org/10.1002/cncr.20618]
[8]
Zhang R, Xia LQ, Lu WW, Zhang J, Zhu JS. LncRNAs and cancer. Oncol Lett 2016; 12(2): 1233-9.
[http://dx.doi.org/10.3892/ol.2016.4770] [PMID: 27446422]
[9]
Reddy KB. MicroRNA (miRNA) in cancer. Cancer Cell Int 2015; 15(1): 38.
[http://dx.doi.org/10.1186/s12935-015-0185-1] [PMID: 25960691]
[10]
Xue M, Zhuo Y, Shan B. MicroRNAs, long noncoding RNAs, and their functions in human disease. Methods Mol Biol 2017; 1617: 1-25.
[http://dx.doi.org/10.1007/978-1-4939-7046-9_1] [PMID: 28540673]
[11]
Peng W-X, Koirala P, Mo Y-Y. LncRNA-mediated regulation of cell signaling in cancer. Oncogene 2017; 36(41): 5661-7.
[http://dx.doi.org/10.1038/onc.2017.184] [PMID: 28604750]
[12]
Hai B, Pan X, Du C, et al. LncRNA XIST promotes growth of human chordoma cells by regulating miR-124-3p/iASPP pathway. OncoTargets Ther 2020; 13: 4755-65.
[http://dx.doi.org/10.2147/OTT.S252195] [PMID: 32547104]
[13]
Bell D, Raza SM, Bell AH, Fuller GN, DeMonte F. Whole-transcriptome analysis of chordoma of the skull base. Virchows Arch 2016; 469(4): 439-49.
[http://dx.doi.org/10.1007/s00428-016-1985-y] [PMID: 27401718]
[14]
Xu Y, Yu X, Zhang M, et al. Promising advances in LINC01116 related to cancer. Front Cell Dev Biol 2021; 9: 736927.
[http://dx.doi.org/10.3389/fcell.2021.736927] [PMID: 34722518]
[15]
Hu H, Chen Q, Ding SJERMPS. LncRNA LINC01116 competes with miR-145 for the regulation of ESR1 expression in breast cancer. Eur Rev Med Pharmacol Sci 2018; 22(7): 1987-93.
[16]
Su X, Zhang J, Luo X, Yang W, Liu Y, Liu Y, et al. LncRNA LINC01116 promotes cancer cell proliferation, migration and invasion in gastric cancer by positively interacting with lncRNA CASC11. OncoTargets Ther 2019; 12(7): 8117-23.
[17]
Fang Y, Huang Z, Li H, Tan W, Zhang Q, Wang L, et al. LINC01116 promotes the progression of epithelial ovarian cancer via regulating cell apoptosis. Eur Rev Med Pharmacol Sci 2018; 22(16): 5127-33.
[18]
Liu W, Liang F, Yang G, Xian L. LncRNA LINC01116 sponges miR-93-5p to promote cell invasion and migration in small cell lung cancer. BMC Pulm Med 2021; 21(1): 50.
[http://dx.doi.org/10.1186/s12890-020-01369-3] [PMID: 33535997]
[19]
Wu J, Chen Z, Zhang L, Cao J, Li X, Gong Z. Knockdown of LINC01116 inhibits cell migration and invasion in head and neck squamous cell carcinoma through epithelial‐mesenchymal transition pathway. J Cell Biochem 2020; 121(1): 867-75.
[http://dx.doi.org/10.1002/jcb.29331]
[20]
Duan Z, Choy E, Nielsen GP, et al. Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in Met expression. J Orthop Res 2010; 28(6): 746-52.
[http://dx.doi.org/10.1002/jor.21055] [PMID: 20041488]
[21]
Huang W, Yan YG, Wang WJ, et al. Development and validation of a 6-miRNA prognostic signature in spinal chordoma. Front Oncol 2020; 10: 556902.
[http://dx.doi.org/10.3389/fonc.2020.556902] [PMID: 33194623]
[22]
Bayrak OF, Gulluoglu S, Aydemir E, et al. MicroRNA expression profiling reveals the potential function of microRNA-31 in chordomas. J Neurooncol 2013; 115(2): 143-51.
[http://dx.doi.org/10.1007/s11060-013-1211-6] [PMID: 23912551]
[23]
Gulluoglu S, Tuysuz EC, Kuskucu A, et al. The potential function of microRNA in chordomas. Gene 2016; 585(1): 76-83.
[http://dx.doi.org/10.1016/j.gene.2016.03.032] [PMID: 27016303]
[24]
Zhang H, Yang K, Ren T, Huang Y, Tang X, Guo W. miR-16-5p inhibits chordoma cell proliferation, invasion and metastasis by targeting Smad3. Cell Death Dis 2018; 9(6): 680.
[http://dx.doi.org/10.1038/s41419-018-0738-z] [PMID: 29880900]
[25]
Zhang K, Liu Z, Wang Z, et al. Long Non-Coding RNA MDFIC-7 promotes chordoma progression through modulating the miR-525-5p/ARF6 axis. Front Oncol 2021; 11: 743718.
[http://dx.doi.org/10.3389/fonc.2021.743718] [PMID: 34621682]
[26]
López-Urrutia E, Bustamante Montes LP, Ladrón de Guevara Cervantes D, Pérez-Plasencia C, Campos-Parra AD. Crosstalk between long non-coding RNAs, Micro-RNAs and mRNAs: Deciphering molecular mechanisms of master regulators in cancer. Front Oncol 2019; 9: 669.
[http://dx.doi.org/10.3389/fonc.2019.00669] [PMID: 31404273]
[27]
Qi X, Zhang DH, Wu N, Xiao JH, Wang X, Ma W. ceRNA in cancer: Possible functions and clinical implications. J Med Genet 2015; 52(10): 710-8.
[http://dx.doi.org/10.1136/jmedgenet-2015-103334] [PMID: 26358722]
[28]
Jiang L, Cheng C, Ji W, et al. LINC01116 promotes the proliferation and invasion of glioma by regulating the microRNA 744 5p MDM2 p53 axis. Mol Med Rep 2021; 23(5): 366.
[http://dx.doi.org/10.3892/mmr.2021.12005] [PMID: 33760190]
[29]
Huang T, Cai M, Chen C, et al. LINC01116 boosts the progression of pituitary adenoma via regulating miR-744–5p/HOXB8 pathway. Mol Cell Endocrinol 2021; 536: 111350.
[http://dx.doi.org/10.1016/j.mce.2021.111350] [PMID: 34098015]
[30]
Cui L, Chen S, Wang D, Yang Q. LINC01116 promotes proliferation and migration of endometrial stromal cells by targeting FOXP1 via sponging miR-9-5p in endometriosis. J Cell Mol Med 2021; 25(4): 2000-12.
[http://dx.doi.org/10.1111/jcmm.16039] [PMID: 33372387]
[31]
Bi C, Cui H, Fan H, Li L. LncRNA LINC01116 promotes the development of colorectal cancer by targeting miR-9-5p/STMN1. OncoTargets Ther 2020; 13: 10547-58.
[http://dx.doi.org/10.2147/OTT.S253532] [PMID: 33116633]
[32]
Chen H, Zhang K, Lu J, Wu G, Yang H, Chen KJO. Comprehensive analysis of mRNA-lncRNA co-expression profile revealing crucial role of imprinted gene cluster DLK1-MEG3 in chordoma. Oncotarget 2017; 8(68): 112623-35.
[http://dx.doi.org/10.18632/oncotarget.22616]
[33]
Bai J, Zhai Y, Wang S, Li M, Zhang S, Li C, et al. LncRNA and mRNA expression profiles reveal the potential roles of lncRNA contributing to regulating dural penetration in clival chordoma. Aging 2020; 12(11): 10809-26.
[http://dx.doi.org/10.18632/aging.103294]
[34]
O’Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol 2018; 9: 409.
[35]
Temel Y, Santegoeds RGC, Yakkioui Y, Jahanshahi A, Hoogland G, van Overbeeke JJ. Validation of reference genes in human chordoma. Surg Neurol Int 2017; 8(1): 100.
[http://dx.doi.org/10.4103/sni.sni_399_16] [PMID: 28695047]
[36]
Ganapathy-Kanniappan S, Geschwind JFH. Tumor glycolysis as a target for cancer therapy: Progress and prospects. Mol Cancer 2013; 12(1): 152.
[http://dx.doi.org/10.1186/1476-4598-12-152] [PMID: 24298908]
[37]
Chen JY, Xu LF, Hu HL, Wen YQ, Chen D, Liu WH. MiRNA-215-5p alleviates the metastasis of prostate cancer by targeting PGK1. Eur Rev Med Pharmacol Sci 2020; 24(2): 639-46.
[PMID: 32017004]
[38]
Beaver LM, Kuintzle R, Buchanan A, et al. Long noncoding RNAs and sulforaphane: A target for chemoprevention and suppression of prostate cancer. J Nutr Biochem 2017; 42: 72-83.
[http://dx.doi.org/10.1016/j.jnutbio.2017.01.001] [PMID: 28131897]
[39]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[40]
Wang CB, Wang Y, Wang JJ, Guo XL. LINC00662 triggers malignant progression of chordoma by the activation of RNF144B via targeting miR-16-5p. Eur Rev Med Pharmacol Sci 2020; 24(3): 1007-22.
[PMID: 32096180]
[41]
Meng L, Xing Z, Guo Z, Liu ZJCD. LINC01106 post-transcriptionally regulates ELK3 and HOXD8 to promote bladder cancer progression. Cell Death & Dis 2020; 11(12): 1-15.
[42]
Zeng L, Lyu X, Yuan J, Wang W, Zhao N, Liu B, et al. Long non-coding RNA LINC01116 is overexpressed in lung adenocarcinoma and promotes tumor proliferation and metastasis. Am J Transl Res 2020; 12(8): 4302-13.
[43]
Zhang Z, Xu H, Hu W, Hu T, Wang XJERMPS. LINC01116 promotes proliferation, invasion and migration of osteosarcoma cells by silencing p53 and EZH2. Eur Rev Med Pharmacol Sci 2019; 23(16): 6813-23.
[44]
Wong RSY. Apoptosis in cancer: From pathogenesis to treatment. J Exp Clin Cancer Res 2011; 30(1): 87.
[http://dx.doi.org/10.1186/1756-9966-30-87] [PMID: 21943236]
[45]
Chen J, Yuan ZH, Hou XH, Shi MH, Jiang R. LINC01116 promotes the proliferation and inhibits the apoptosis of gastric cancer cells. Eur Rev Med Pharmacol Sci 2020; 24(4): 1807-14.
[PMID: 32141549]
[46]
Fan X, Sun Y, Guo X, He C, Han B, Sun XJCB. Long non-coding RNA LINC01116 regulated miR-744-5p/SCN1B axis to exacerbate lung squamous cell carcinoma. Cancer Biomark 2020; 28(4): 1-10.
[47]
Wang J, Gao J, Chen Q, et al. LncRNA LINC01116 Contributes to Cisplatin Resistance in Lung Adenocarcinoma. OncoTargets Ther 2020; 13: 9333-47.
[http://dx.doi.org/10.2147/OTT.S244879] [PMID: 33061421]
[48]
Shang B, Li Z, Li M, et al. Silencing LINC01116 suppresses the development of lung adenocarcinoma via the AKT signaling pathway. Thorac Cancer 2021; 12(14): 2093-103.
[http://dx.doi.org/10.1111/1759-7714.14042] [PMID: 34061456]
[49]
Suhaili SH, Karimian H, Stellato M, Lee TH, Aguilar MI. Mitochondrial outer membrane permeabilization: A focus on the role of mitochondrial membrane structural organization. Biophys Rev 2017; 9(4): 443-57.
[http://dx.doi.org/10.1007/s12551-017-0308-0] [PMID: 28823106]
[50]
Shamas-Din A, Kale J, Leber B, Andrews DW. Mechanisms of action of Bcl-2 family proteins. Cold Spring Harb Perspect Biol 2013; 5(4): a008714.
[http://dx.doi.org/10.1101/cshperspect.a008714] [PMID: 23545417]
[51]
Williams GH, Stoeber K. The cell cycle and cancer. J Pathol 2012; 226(2): 352-64.
[http://dx.doi.org/10.1002/path.3022]
[52]
Matthews HK, Bertoli C, de Bruin RAM. Cell cycle control in cancer. Nat Rev Mol Cell Biol 2022; 23(1): 74-88.
[http://dx.doi.org/10.1038/s41580-021-00404-3] [PMID: 34508254]
[53]
Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature 2001; 411(6835): 342-8.
[http://dx.doi.org/10.1038/35077213] [PMID: 11357141]
[54]
Yang J, Ren B, Yang G, et al. The enhancement of glycolysis regulates pancreatic cancer metastasis. Cell Mol Life Sci 2020; 77(2): 305-21.
[http://dx.doi.org/10.1007/s00018-019-03278-z] [PMID: 31432232]
[55]
Akram M. Mini-review on glycolysis and cancer. J Cancer Educ 2013; 28(3): 454-7.
[http://dx.doi.org/10.1007/s13187-013-0486-9] [PMID: 23728993]
[56]
Bowler MW. Conformational dynamics in phosphoglycerate kinase, an open and shut case? FEBS Lett 2013; 587(13): 1878-83.
[http://dx.doi.org/10.1016/j.febslet.2013.05.012] [PMID: 23684636]
[57]
Chen Z, Tao Q, Qiao B. Silencing of LINC01116 suppresses the development of oral squamous cell carcinoma by up-regulating microRNA-136 to inhibit FN1. Cancer Manag Res 2019; 11: 6043-59.
[58]
Yuan W, Sun H, Yu LJB. Long non-coding RNA LINC01116 accelerates the progression of keloid formation by regulating miR-203/SMAD5 axis. Burns 2021; 47(3): 665-1675.
[59]
Wang L, Cui M, Cheng D, et al. miR-9-5p facilitates hepatocellular carcinoma cell proliferation, migration and invasion by targeting ESR1. Mol Cell Biochem 2021; 476(2): 575-83.
[http://dx.doi.org/10.1007/s11010-020-03927-z] [PMID: 33106914]
[60]
Zhu K, Lin J, Chen S, Xu Q. miR-9-5p promotes lung adenocarcinoma cell proliferation, migration and invasion by targeting ID4. Technol Cancer Res Treat 2021; 20.
[http://dx.doi.org/10.1177/15330338211048592] [PMID: 34723712]
[61]
Chen L, Hu W, Li G, Guo Y, Wan Z, Yu J. Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13. Cell Mol Biol Lett 2019; 24(1): 20.
[http://dx.doi.org/10.1186/s11658-019-0145-1] [PMID: 30899277]
[62]
Ying M, Feng H, Zhang X, Liu R, Ning H. MiR-9-5p inhibits the proliferation, migration and invasion of choroidal melanoma by targeting BRAF. Technol Cancer Res Treat 2020; 19.
[http://dx.doi.org/10.1177/1533033820956987] [PMID: 33138697]
[63]
Wang J, Wang B, Ren H, Chen W. miR-9-5p inhibits pancreatic cancer cell proliferation, invasion and glutamine metabolism by targeting GOT1. Biochem Biophys Res Commun 2019; 509(1): 241-8.
[http://dx.doi.org/10.1016/j.bbrc.2018.12.114] [PMID: 30591220]
[64]
Babion I, Jaspers A, van Splunter AP, van der Hoorn IAE, Wilting SM, Steenbergen RDM. miR-9-5p exerts a dual role in cervical cancer and targets transcription factor TWIST1. Cells 2019; 9(1): 65.
[http://dx.doi.org/10.3390/cells9010065] [PMID: 31888045]
[65]
Yoon JH, Abdelmohsen K, Gorospe M. Functional interactions among microRNAs and long noncoding RNAs. Semin Cell Dev Biol 2014; 34: 9-14.
[http://dx.doi.org/10.1016/j.semcdb.2014.05.015] [PMID: 24965208]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy